糖尿病性臓器障害のエネルギ－変化と遺伝子異常

• 研究課題/領域番号: 23602012
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 医学物理学・放射線技術学
• 研究機関: 新潟薬科大学
• 研究代表者: 渡邊 賢一 新潟薬科大学, 薬学部, 教授 (70175090)
• 研究期間 (年度): 2011 – 2013
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 5,460千円 (直接経費: 4,200千円、間接経費: 1,260千円); 2013年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円); 2012年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2011年度: 2,600千円 (直接経費: 2,000千円、間接経費: 600千円)
• キーワード: 標識脂肪酸 / 医療薬剤学 / 糖尿病 / 臓器障害 / 酸化ストレス / 小胞体ストレス / 遺伝子変化 / アポト－シス / 心臓 / 腎臓 / エネルギ－ / 国際情報交流 / インド / インドネシア / アメリカ合衆国 / 中国

研究概要

糖尿病性腎症・心筋症や不全心筋のエネルギ－変化を画像化することを目的とした。　脂肪酸代謝機能を評価する標識薬剤として [I-131]9MPA を, 糖代謝機能を評価する薬剤として [C-14]2DG を、交感神経機能として[I-125]MIBGをそれぞれ用いた。　心不全モデルラット・糖尿病モデルDN14－3－3トランスジェニックマウスを作成し、代謝異常と遺伝子異常を検討中した。
その結果、糖尿病性腎症では酸化ストレスが亢進し、クルクミンなどの機能性食品投与でそれらが改善した。

研究成果

• [雑誌論文] Olmesartan protects against oxidative stress possibly through the Nrf2 signaling pathway and inhibits inflammation in daunorubicin-induced nephrotoxicity in rats (2014)
  • 著者名/発表者名: Vengadeshprabhu Karuppa Gounder, Watanabe K et al.
  • 雑誌名: International Immuno pharmacology 巻: 18 ページ: 282-289
• [雑誌論文] Olmesartan protects against oxidative stress possibly through the Nrf2 signaling pathway and inhibits inflammation in daunorubicin-induced nephrotoxicity in rats. (2014)
  • 著者名/発表者名: Vengadeshprabhu Karuppa Gounder, Kenichi Watanabe et al.
  • 雑誌名: International Immunopharmacology. 巻: 18 ページ: 282-289
  • 査読あり
• [雑誌論文] Curcumin decreases renal triglyceride accumulation through AMPK–SREBP signaling (2013)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 雑誌名: J Nutriti Biochem 巻: 24 ページ: 796-802
• [雑誌論文] Molecular understanding of curcumin in diabetic nephropathy (2013)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 雑誌名: Drug Discovery Today 巻: 18 ページ: 756-763
• [雑誌論文] Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap 1 pathway (2013)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 雑誌名: Mol Nutr Food Res. 巻: 57 ページ: 1649-1659
• [雑誌論文] The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic non-obese type 2 diabetic rats : A differential role of unfolded protein response (UPR) signaling proteins (2013)
  • 著者名/発表者名: Arun P L, Watanabe K et al.
  • 雑誌名: Int J Bioch Cell Bio. 巻: 45 ページ: 438-447
• [雑誌論文] Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK mediated apoptosis (2013)
  • 著者名/発表者名: Somasundaram Arumugam, Watanabe K et al.
  • 雑誌名: Cardiovascular Therapeutics 巻: 31 ページ: 352-362
• [雑誌論文] A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. (2013)
  • 著者名/発表者名: Fujii M, Kenichi Watanabe et al.
  • 雑誌名: Med Mol Morphol. 巻: in press 号: 3 ページ: 141-152
  • DOI: 10.1007/s00795-013-0016-1
  • NAID: 10031203181
  • 査読あり
• [雑誌論文] Curcumin decreases renal triglyceride accumulation through AMPK–SREBP signaling. (2013)
  • 著者名/発表者名: Vivian Soetikno, Kenichi Watanabe et al.
  • 雑誌名: J Nutriti Biochem. 巻: 24 ページ: 796-802
  • 査読あり
• [雑誌論文] Molecular understanding of curcumin in diabetic nephropathy. (2013)
  • 著者名/発表者名: Vivian Soetikno, Kenichi Watanabe et al.
  • 雑誌名: Drug Discovery Today. 巻: 18 ページ: 756-763
  • 査読あり
• [雑誌論文] Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap 1 pathway. (2013)
  • 著者名/発表者名: Vivian Soetikno, Kenichi Watanabe et al.
  • 雑誌名: Mol Nutr Food Res. 巻: 57 ページ: 1649-1659
  • 査読あり
• [雑誌論文] The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic non-obese type 2 diabetic rats: A differential role of unfolded protein response (UPR) signaling proteins. (2013)
  • 著者名/発表者名: Arun P L, Kenichi Watanabe et al.
  • 雑誌名: Int J Bioch Cell Bio. 巻: 45 ページ: 438-447
  • 査読あり
• [雑誌論文] Mulberry leaf diet protects against progression of experimental autoimmune myocarditis to dilated cardiomyopathy via modulation of oxidative stress and MAPK mediated apoptosis. (2013)
  • 著者名/発表者名: Somasundaram Arumugam, Kenichi Watanabe et al.
  • 雑誌名: Cardiovascular Therapeutics. 巻: 31 ページ: 352-362
  • 査読あり
• [雑誌論文] Role of protein kinase C-MAPK, oxidative stress and inflammation pathways in diabetic nephropathy (2012)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 雑誌名: Nephrology & Therapeutics 巻: S2 ページ: 1-9
• [雑誌論文] Curcumin Prevents Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats : Possible Involvement of PKC-MAPK Signaling Pathway (2012)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 雑誌名: Eur J Pharm Sci. 巻: 47 ページ: 604-614
• [雑誌論文] Involvement of AMPK and MAPK signaling during the progression of experimental autoimmune myocarditis in rats and its blockade using a novel antioxidant (2012)
  • 著者名/発表者名: Arumugam S, Thandavarayan RA, Watanabe K et al.
  • 雑誌名: Experimental and Molecular Pathology 巻: 93 ページ: 183-189
• [雑誌論文] Telmisartan acts through the modulation of ACE-2/ANG 1-7/masR in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis (2012)
  • 著者名/発表者名: Vijayakumar S, Watanabe K et al.
  • 雑誌名: Life Sciences 巻: 90 ページ: 289-300
• [雑誌論文] Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor (2012)
  • 著者名/発表者名: Vijayakumar Sukumaran, Watanabe K et al.
  • 雑誌名: Molecular and Cellular Endocrinology 巻: 351 ページ: 208-219
• [雑誌論文] Nootropic activity of acetaminophen against colchicines induced cognitive impairment in rats (2012)
  • 著者名/発表者名: Vigneshwaran Pitchaimani, Watanabe K et al.
  • 雑誌名: J Clin Biochem Nutri 巻: 50 ページ: 241-244
  • NAID: 130004879275
• [雑誌論文] Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats : Involvement of ACE2-Ang (1-7)-mas axis (2012)
  • 著者名/発表者名: Arumugam S, Watanabe K et al.
  • 雑誌名: Toxicology 巻: 291 ページ: 139-145
• [雑誌論文] Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signaling (2012)
  • 著者名/発表者名: Arumugam S, Watanabe K et al.
  • 雑誌名: Free Radic Res. 巻: 46 ページ: 154-163
• [雑誌論文] Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice (2012)
  • 著者名/発表者名: Arun Prasath Lakshmanan, Watanabe K et al.
  • 雑誌名: Molecular and Cellular Endocrinology 巻: 348 ページ: 104-111
• [雑誌論文] Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy (2012)
  • 著者名/発表者名: Somasundaram Arumugam, Watanabe K et al.
  • 雑誌名: Journal of Cellular and Molecular Medicine 巻: 16 ページ: 2176-2185
• [雑誌論文] Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in Experimental Autoimmune Myocarditis rats (2012)
  • 著者名/発表者名: Somasundaram Arumugam, Watanabe K et al.
  • 雑誌名: J Clin Biochem Nutr. 巻: 50 ページ: 139-144
  • NAID: 130004466682
• [雑誌論文] Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats (2012)
  • 著者名/発表者名: Arun P L, Watanabe K et al.
  • 雑誌名: Biochemical Pharmacology 巻: 83 ページ: 653-660
• [雑誌論文] Curcumin Prevents Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats (2012)
  • 著者名/発表者名: Vivian S, K Watanabe et al.
  • 雑誌名: Eur J Pharm Sci. 巻: 47 ページ: 604-614
  • 査読あり
• [雑誌論文] Involvement of AMPK and MAPK signaling during the progression of experimental autoimmune myocarditis in rats and its blockade using a novel antioxidant. (2012)
  • 著者名/発表者名: Arumugam S, Watanabe K et al.
  • 雑誌名: Experimental and Molecular Pathology. 巻: 93 ページ: 183-189
  • 査読あり
• [雑誌論文] Telmisartan acts through the modulation of ACE-2/ANG 1-7/masR in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis (2012)
  • 著者名/発表者名: Vijayakumar S, K Watanabe et al.
  • 雑誌名: Life Sciences. 巻: 90 ページ: 289-300
  • 査読あり
• [雑誌論文] Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor (2012)
  • 著者名/発表者名: Vijayakumar S, K Watanabe.
  • 雑誌名: Molecular and Cellular Endocrinology. 巻: 351 ページ: 208-219
  • 査読あり
• [雑誌論文] Nootropic activity of acetaminophen against colchicines induced cognitive impairment in rats. (2012)
  • 著者名/発表者名: Vigneshwaran P, K Watanabe et al.
  • 雑誌名: J Clin Biochem Nutri. 巻: 50 ページ: 241-244
  • NAID: 130004879275
  • 査読あり
• [雑誌論文] Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: Involvement of ACE2-Ang (1-7)-mas axis. (2012)
  • 著者名/発表者名: .Arumugam S, Watanabe K et al.
  • 雑誌名: Toxicology. 巻: 291 ページ: 139-145
  • 査読あり
• [雑誌論文] Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signaling (2012)
  • 著者名/発表者名: Arumugam S, Watanabe K et al.
  • 雑誌名: Free Radic Res 巻: ;46, ページ: 154-163
  • 査読あり
• [雑誌論文] Quercetin offers cardioprotection against progression of experimental autoimmune myocarditis by suppression of oxidative and endoplasmic reticulum stress via endothelin-1/MAPK signaling. (2012)
  • 著者名/発表者名: Arumugam S, Watanabe K, et al.
  • 雑誌名: Free Radic Res. 巻: 46 ページ: 154-163
  • 査読あり
• [雑誌論文] Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats. (2012)
  • 著者名/発表者名: Arun P, Watanabe K, et al.
  • 雑誌名: Biochemical Pharmacology 巻: 83 ページ: 653-660
  • 査読あり
• [雑誌論文] Curcumin attenuates diabetic nephropathy by inhibiting PKC-a and PKC-b1 activity in streptozotocin-induced type 1 diabetic rats. (2011)
  • 著者名/発表者名: Vivian S, Kenichi Watanabe,et al.
  • 雑誌名: Mol Nutr Food Res. 巻: 55 ページ: 1655-1665
  • 査読あり
• [雑誌論文] Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action. (2011)
  • 著者名/発表者名: Arun P, Kenichi Watanabe,et al.
  • 雑誌名: Free Radic Res. 巻: 45 ページ: 575-84
  • 査読あり
• [雑誌論文] Telmisartan prevents the progression of renal injury in daunorubicin rats with the alteration of angiotensin II and endothelin-1 receptor expression associated with its PPAR- agonist actions. (2011)
  • 著者名/発表者名: Wawaimuli A, Watanabe K et al.
  • 雑誌名: Toxicology. 巻: 279 ページ: 91-99
  • 査読あり
• [学会発表] The PERK-CHOP/GADD153 axis is the major determinant rather than the IRE-1α-JNK for the ER stress-induced myocardial apoptosis in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats (2014)
  • 著者名/発表者名: Arun Prasath Lakshmanan, Watanabe K et al.
  • 学会等名: SINGAPORE CARDIAC SOCIETY 24TH ANNUAL MEETING
  • 発表場所: Singapore
• [学会発表] Development of Heart Failure after Cardiac Myosin-Induced Experimental Autoimmune Myocarditis in Rats (2014)
  • 著者名/発表者名: Somasundaram A, Kenichi WATANABE et al.
  • 学会等名: 日本循環器学会
  • 発表場所: 東京国際フォ－ラム
• [学会発表] Dominant Negative Mutation of Myocardial 14-3-3eta Protein and Its Effect on LAD ligation induced Acute Myocardial Infarction in mice (2013)
  • 著者名/発表者名: Arumugam S, Watanabe K et al.
  • 学会等名: 第77回日本循環器学会
  • 発表場所: 東京横浜
  • 招待講演
• [学会発表] Fasting mediated predisposition of insulin induced hypoglycemic seizures is independent of hippocampal signaling of insulin (2013)
  • 著者名/発表者名: Vigneshwaran Pitchaimani, Watanabe K et al.
  • 学会等名: Colloquium on Drug Resistant Epilepsy
  • 発表場所: India
• [学会発表] Fasting mediated predisposition of insulin induced hypoglycemic seizures is independent of central hippocampus insulin signaling mechanism (2013)
  • 著者名/発表者名: Vigneshwaran Pitchaimani, Watanabe K et al.
  • 学会等名: The 36^<th> Naito Conference Molecular Aspects of Energy Balance and Feeding Behavior
  • 発表場所: SAPPORO, Japan
• [学会発表] Modulation of HMGB1/RAGE-NFκB cascade plays crucial role for the pathogenesis of atopic dermatitis in transgenic NC/Nga mice (2013)
  • 著者名/発表者名: Vengadeshprabhu KaruppaGounder, Watanabe K et al.
  • 学会等名: The 3rd International Science Congress
  • 発表場所: India
• [学会発表] Modulation of HMGB1/RAGE-NFκB cascade plays crucial role for the pathogenesis of atopic dermatitis in transgenic NC/Nga mice (2013)
  • 著者名/発表者名: Karuppa Gounder Vengadeshprabhu , Kenichi WATANABE et al.
  • 学会等名: The 3rd International Science Congress 2013 India
  • 発表場所: India
• [学会発表] Fasting predisposes insulin induced hypoglycemic seizures by failure of counter regulatory response mechanism (2013)
  • 著者名/発表者名: Vigneshwaran PITCHAIMANI, Kenichi WATANABE et al.
  • 学会等名: Indo-American Epilepsy Symposium
  • 発表場所: Kovai Medical Center India
• [学会発表] Exacerbation of Endoplasmic Reticulum Stress-Related Maladaptive Cardiac Remodeling in Pressure-Overloaded Dominant Negative 14-3-3eta Mice (2012)
  • 著者名/発表者名: Flori Ratna Sari, Watanabe K.
  • 学会等名: 第76回日本循環器学会
  • 発表場所: 福岡
• [学会発表] Olmesartan attenuates the development of heart failure after experimental autoimmune myocarditis in rats through the modulation of ANG 1-7 mas receptor (2012)
  • 著者名/発表者名: Vijayakumar Sukumaran, Watanabe K et al.
  • 学会等名: 第76回日本循環器学会
  • 発表場所: 福岡
• [学会発表] ROLE OF 14-3-3 PROTEIN AGAINST ISCHEMIC INSULT IN THE MICE HEART SUBJECTED TO MYOCARDIAL INFARCTION (2012)
  • 著者名/発表者名: Somasundaram A, Watanabe K et al.
  • 学会等名: EUROPEAN CARDIOLOGICAL SOCIETY–HEART FAILURE
  • 発表場所: Serbia
• [学会発表] Amelioration of Liver Injury by Curcumin in Streptozotocin Induced-Diabetic Rats (2012)
  • 著者名/発表者名: Vivian Soetikno, Watanabe K et al.
  • 学会等名: Internetion Confernce on Medical and Pharmaceutical Sciences (ICMPS'2012)
  • 発表場所: Bangkok (Thailand)
• [学会発表] Endoplasmic reticulum stress in cardic hypertrophy; role of 14-3-3 protein and p38 MAPK pathway (2011)
  • 著者名/発表者名: Flori Sari, Watanabe K.
  • 学会等名: 第51回新潟心不全研究会
  • 発表場所: 新潟
  • 年月日: 2011-06-16
• [学会発表] Olmesartan, an AT1 antagonist, attenuates cardiac oxidative induced by experimental autoimmune myocarditis (2011)
  • 著者名/発表者名: Vijyaakumar Sukumaran, Watanabe K et al.
  • 学会等名: 75^<th> Annual Scientific meeting of the Japanese Circulation Society (JCS2011)
  • 発表場所: 横浜
• [学会発表] Telmisartan Inhibits the Progression of Cardiomyopathy in Daunorubicin Rats with the Alteration of Advance Glycation End Products (2011)
  • 著者名/発表者名: Wawaimuli Arozal, Watanabe K et al.
  • 学会等名: 75^<th> Annual Scientific meeting of the Japanese Circulation Society (JCS2011)
  • 発表場所: 横浜
• [学会発表] Modulation of Endoplasmic Reticulum Stress And Cardiomyocyte Apoptosis By Mulberry Leaf Diet In Experimental Autoimmune Myocarditis Rats (2011)
  • 著者名/発表者名: Somasundaram ARUMUGAM, Watanabe K et al.
  • 学会等名: 6th ICCD
  • 発表場所: NewDelhi. India
• [学会発表] Protective roles of 14-3-3 protein against endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis in diabetic heart (2011)
  • 著者名/発表者名: Flori R. Sari, Watanabe K et al.
  • 学会等名: 10^<th> Diabetes Asia
  • 発表場所: Kuala Lumpur, Malaysia
• [学会発表] Free radical scavenger protects against complications in heart and kidney by attenuating oxidative and endoplasmic reticulum stress in diabetic mice (2011)
  • 著者名/発表者名: Flori R. Sari, Watanabe K et al.
  • 学会等名: 10^<th> Diabetes Asia
  • 発表場所: Kuala Lumpur, Malaysia
• [学会発表] Endoplasmic reticulum stress induces cardiomyocyte apoptosis during pathological cardiac hypertrophy through the p38 MAPK pathway (2011)
  • 著者名/発表者名: Flori R. Sari, Watanabe K et al.
  • 学会等名: 28^<th> ISHR
  • 発表場所: Kuala Lumpur, Malaysia
• [図書] Diabetic cardiomyopathy and oxidative stress. Diabetes -Oxidative Stress and Dietary Antioxidants (2013)
  • 著者名/発表者名: Somasundaram Arumugam, Watanabe K et al.
  • 出版者: Victor R Preedy.Elsevier
• [図書] Vimentin-positive profibrogenic mesenchynal cells in intestine : Promising therapeutic targets for intestinal fibrosis. In Vimentin Concepts and Molecular Mechanisms (2013)
  • 著者名/発表者名: K Suzuki, K Watanabe, et al.
  • 出版者: Nova Science Publishers Inc.
• [図書] Diabetes-Oxidative Stress and Dietary Antioxidants. (2013)
  • 著者名/発表者名: Somasundaram Arumugam, Kenichi Watanabe et al.
  • 出版者: Elsevier
• [図書] Vimentin-positive profibrogenic mesenchynal cells in intestine: Promising therapeutic targets for intestinal fibrosis. (2013)
  • 著者名/発表者名: K Suzuki, K Watanabe, et al.
  • 出版者: Nova Science Publishers Inc.
• [図書] Histopathology of experimental autoimmune myocarditis. Advances in Medicine and Biology. Vol 37. Chapter-3 (2012)
  • 著者名/発表者名: Watanabe K et al.
  • 出版者: Nova Science Pub Inc.
• [図書] Diabetic cardiomyopathy : Role of renin angiotensin system, Angiotensin New Research (2012)
  • 著者名/発表者名: Watanabe K et al.
  • 出版者: Nova Science Publishers Inc.
• [図書] Aldosterone antagonist and diuretics for heart failure. Advances in Medicine and Biology. Vol29 (2012)
  • 著者名/発表者名: Watanabe K et al.
  • 出版者: Science Publishers Inc.